This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue is the most prevalent mosquito-borne viral disease in humans. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the life-threatening forms of severe dengue virus (DENV) infection, are manifested by increased vascular permeability and plasma leakage. Available evidence indicates that infection of human monocytes/macrophages results in a dramatic increase in production of inflammatory cytokines and other immune mediators, which act on vascular endothelium and cause alteration of endothelial permeability. However, how such cellular responses are regulated and how such regulations contribute to the unique feature of DHF/DSS pathogenesis are unclear. Recently, it was demonstrated that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, play important roles in most cellular and developmental processes, and deregulation of miRNA expression is associated with many human diseases. The central hypothesis of this study is that miRNAs may serve as the essential factors that modulate cellular responses of human monocytes/macrophages and vascular endothelial cells in DENV infection. To address this, miRNA expression profiling in DENV-infected monocytes/macrophages and vascular endothelial cells, and vascular endothelial cells that are treated with the immune mediators released from infected monocytes/macrophages, will be performed and analyzed. Regulatory roles of miRNAs in the pathogenic process of DHF and DSS will be further characterized. The findings from this study will help to clarify critical cellular responses in DENV infection, and provide valuable insights into the molecular mechanism of DHF immunopathogenesis. Such findings may uncover new strategies for the prevention and possibly treatment of DHF/DSS.